Steroidogenesis

Steroid hormones are derivatives of cholesterol that are synthesized by a variety of tissues, most prominently the adrenal gland and gonads. The cholesterol precursor comes from cholesterol synthesized within the cell from acetate, from cholesterol ester stores in intracellular lipid droplets or from uptake of cholesterol-containing low density lipoproteins. Lipoproteins taken up from plasma are most important when steroidogenic cells are chronically stimulated.

The basic cyclopentanoperhydrophenanthrene ring structure and carbon numbering system of all steroid hormones is depicted to the right, using pregnenolone as an example. Pregnenolone is an example of what is called a "C-21 steroid" because it has 21 carbons. Similarly, a steroid such as testosterone (see below) is referred to as a "C-19 steroid".

Biosynthesis of steroid hormones requires a battery of oxidative enzymes located in both mitochondria and endoplasmic reticulum. The rate-limiting step in this process is the transport of free cholesterol from the cytoplasm into mitochondria. Within mitochondria, cholesterol is converted to pregnenolone by an enzyme in the inner membrane called CYP11A1. Pregnenolone itself is not a hormone, but is the immediate precursor for the synthesis of all of the steroid hormones. The following table delineates the enzymes required to synthesize the major classes of steroid hormones.

Common name

"Old" name

Current name

Side-chain cleavage enzyme; desmolase

P450SCC

CYP11A1

3 beta-hydroxysteroid dehydrogenase

3 beta-HSD

3 beta-HSD

17 alpha-hydroxylase/17,20 lyase

P450C17

CYP17

21-hydroxylase

P450C21

CYP21A2

11 beta-hydroxylase

P450C11

CYP11B1

Aldosterone synthase

P450C11AS

CYP11B2

Aromatase

P450aro

CYP19

Typically, endocrinologists classify steroid hormones into five groups of molecules, based primarily on the receptor to which they bind:

Glucocorticoids; cortisol is the major representative in most mammals

Mineralocorticoids; aldosterone being most prominent

Androgens such as testosterone

Estrogens, including estrodiol and estrone

Progestogens (also known a progestins) such as progesterone

The biosynthetic pathways for major representatives of these classes of steroid hormones is depicted in the following diagram. Be aware that a variety of related molecules exist, some of which may have significant effects, particularly in certain pathologic conditions.